Microplastics induce immune suppression via S100A8 downregulation

Microplastic (MP) pollution has been largely reported in the daily consumption of water and food, however, the toxicities of MPs to human beings remain largely uncovered. We found that MPs in drinking water significantly impaired mouse immune function by reducing spleen weight, CD8 T cell amount and raising CD4 to CD8 T cell ratio. We performed proteomics and phosphoproteomics by LC-MS/MS and found MPs significantly induced 130 and 57 proteins upregulated in proteome and phosphoproteome, and 191 and 37 proteins downregulated in proteome and phosphoproteome, separately. Bioinformatic analysis show that asthma, mineral absorption, and the IL-17 signaling pathway were significantly enriched and may be involved in MP-induced spleen damage and immune suppression. We verified the top 3 differentially expressed proteins and phosphoproteins by western blot, and we further showed that S100A8 was significantly downregulated by MPs via histochemistry staining. Our results revealed that MPs can induce spleen damage and immune suppression by reducing S100A8 expression, suggesting an underestimated influence and mechanism of MPs on the mammalian immune system.